The Effect of Probenecid on Urate Transport in the Rat Kidney

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Abstract
The effects of probenecid on net urate transport, urate reabsorption and urate secretion was examined using clearance, microinjection and precession techniques in the rat. The administration of probenecid in a dose of 100 mg/kg body wt per h to mildly diuretic rats results in an increase in the fractional excretion of urate. Of note is the rise in the serum urate concentration which, while of small magnitude, is statistically significant. The increase in urate clearance implies an alteration in urate reabsorption. The urinary recoveries of urate microinjected directly into early or late portions of the proximal convoluted tubule are increased in animals receiving probenecid. This finding indicates a decrease in urate reabsorption in the proximal convoluted tubule and at sites distal to the accessible portion of the proximal tubule. Probenecid also inhibits the secretion of urate from the interstitial fluid into the tubular lumen as evidence by a decrease in the ratio of 14C/3H counts in the 1st urine sample to contain inulin as compared to control animals. Probenecid inhibits both the tubular secretion and reabsorption of urate, the latter effect predominating. The net effect is a marked increase in the urinary excretion of urate.

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